Document Type
Article
Publication Date
3-2015
Publication Title
F1000Research
Volume
4
Issue
65
Pages
1-11
Publisher Name
F1000 Research Ltd.
Abstract
Like many hemoglobins, the structure of the dimeric hemoglobin from the clam Scapharca inaequivalvis is a “closed bottle” since there is no direct tunnel from the oxygen binding site on the heme to the solvent. The proximal histidine faces the dimer interface, which consists of the E and F helicies. This is significantly different from tetrameric vertebrate hemoglobins and brings the heme groups near the subunit interface. The subunit interface is also characterized by an immobile, hydrogen-bonded network of water molecules. Although there is data which is consistent with the histidine gate pathway for ligand escape, these aspects of the structure would seem to make that pathway less likely. Locally enhanced sampling molecular dynamics are used here to suggest alternative pathways in the wild-type and six mutant proteins. In most cases the point mutations change the selection of exit routes observed in the simulations. Exit via the histidine gate is rarely seem although oxygen molecules do occasionally cross over the interface from one subunit to the other. The results suggest that changes in flexibility and, in some cases, creation of new cavities can explain the effects of the mutations on ligand exit paths.
Recommended Citation
Trujillo, Kevin; Papagiannopoulos, Tasso; and Olsen, Kenneth W.. Effects of Mutations on the Molecular Dynamics of Oxygen Escape from the Dimeric Hemoglobin of Scapharca inaequivalvis. F1000Research, 4, 65: 1-11, 2015. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.12688/f1000research.6127.1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Statement
© 2015 Trujillo K et al.
Comments
Author Posting © 2015 Trujillo K et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). http://dx.doi.org/10.12688/f1000research.6127.1